Each year, thousands seek treatment for pain in the temporomandibular joint (TMJ). The cost, both in human suffering and health care resources, is enormous. The goal of this proposal is to establish an animal preparation for the study of TMJ nociceptor physiology. The lack of a physiological model of TMJ joint nociception prevents effective testing of current hypotheses of the etiology of TMJ pain, and limits development and testing of new analgesics. Our initial project focuses on identifying the characteristics and distribution of TMJ nociceptors. Extracellular, single unit recording techniques will be used to characterize the activity of cell bodies of TMJ afferents in the trigeminal ganglion in response to controlled movements of the mandible. The second project attempts to identify the endogenous agents that may be directly involved in the production and maintenance of TMJ pain through their ability to activate and sensitize nociceptors. Other models of joint nociception (cat knee joint) have concentrated on prostaglandin mediated mechanisms of sensitization. Due to the relatively weak affects of aspirin-like drugs, we will concentrate on the affects of non-prostaglandin factors. These will include substances such as interleukin-1, leukotriene B4 and serotonin. These substances have been found in high concentrations in the synovial fluid of painful joints. Through the identification of factors contributing to joint nociceptor activation and sensitization we hope to identify the type of compounds likely to have analgesic activity in the chronically painful TMJ. Contained within the body of these two studies is a comparison of properties of nociceptors in males and females. TMJ pain is reported disproportionately in the female population. A determination of physiological similarities and disimilarities, including receptor distributions, range and propensity to sensitize may clarify etiology and treatment of this gender based disorder.